GDP-fucose:GM1 alpha 1----2fucosyltransferase is activated in parenchymal cells of rat liver during early stages of N-2-acetylaminofluorene induced hepatocarcinogenesis.
Gangliosides from liver parenchymal and non-parenchymal cells were isolated from Fischer 344 rats that had been fed normal diet or a diet supplemented with 0.03% N-2-acetylaminofluorene (AAF) for 4 weeks. Gangliosides from liver cell fractions were characterized by an induction of both II3NeuAcIV3 alpha GalIV2FucGg4 and GM3 synthesis in the parenchymal cells of AAF-fed animals which were missing in parenchymal cells from animals fed normal diet. In addition, new bands corresponding to GM1 and GD1a were observed in cell fractions of AAF-fed animals. The activity of the GM1-specific alpha 1----2fucosyltransferase induced after AAF feeding was found to be enriched 5- to 6-fold in the parenchymal cell fraction of AAF-fed animals and correlated with the parenchymal cell marker enzyme glucose-6-phosphatase in these cell fractions. Feeding animals the hepatotoxin acetaminophen at 1.87% in the diet for 10 weeks resulted in no increase in the levels of the alpha 1----2fucosyltransferase. Antibodies specific for II3NeuAcIV3 alpha GalIV2FucGg4 were produced and utilized in tissue localization studies. These results indicated little or no staining of normal liver tissue or that after acetaminophen feeding was observed. In contrast, focal areas of staining of liver tissue from animals after 3 weeks of 0.03% AAF feeding were readily apparent. These results indicate that induction of alpha 1----2fucosyltransferase and fucoganglioside synthesis is most probably a property of liver parenchymal cells and is associated with events occurring during early stages of AAF-induced carcinogenesis.
Holmes
E H
EH
Pacific Northwest Research Foundation, Seattle, WA 98122.
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002240:Carbohydrate Sequence; D004789:Enzyme Activation; D005647:Fucosyltransferases / Q000378:metabolism*; D006602:Hexosyltransferases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values
D014408:Biomarkers, Tumor; D000082:Acetaminophen; D015073:2-Acetylaminofluorene; D005647:Fucosyltransferases; C037650:GDPfucose-GM1 ganglioside alpha-fucosyltransferase; D006602:Hexosyltransferases